Studies have been aimed at trying to understand mechanisms by which murine leukemia viruses induce erythroid transformation and to understand why some strains of mice are resistant to one or more of the stages of the malignant process. Investigations on the acute erythroleukemia-inducing virus, spleen focus-forming virus(SFFV), have been several-fold. Comparisons of the molecular structure of two variants, SFFV-P and SFFV-A, and formation of a recombinant virus have allowed localization of a region within the envelope gene that determines the ability of infected cells to differentiate in response to erythropoietin. Other experiments have shown that the long terminal repeat (LTR) region of SFFV, unlike Friend murine leukemia virus, does not carry sequences required for tissue-specific induction of leukemia, since a number of different LTRs can be substituted without affecting the disease latency of phenotype. And finally, the generation of helper-free SFFVs using a packaging cell line has provided proof that helper virus is not required for in vitro transformation of erythroid cells, first state acute erythroleukemia in mice or development in vivo of second stage tumorigenic cells. Studies on the genetics of susceptibility to early erythroleukemia induced by Friend murine leukemia virus have identified a gene on chromosome 5, at or near the Rmcf locus, that plays a major role in resistance of mice to this disease by preventing the replication of mink cell focus-inducing (MCF) viruses, believed to be the proximal cause of the disease. This gene is believed to be either a structrual gene or a regulatory gene for an MCF virus-related envelope glycoprotein that appears to block the cell surface receptor for MCF viruses. Additional genes, acting through unknown mechanisms, may also be involved in resistance.